This program has as its goal the synthesis of structurally and biologically interesting natural products through creative application of asymmetric catalytic methodologies. Targets of varying structural and stereochemical complexity are selected to both illustrate and challenge recently discovered methods for enantioselective synthesis, and to inspire development of new catalytic reactions. Bipinnatin I (1) is a recently discovered member of the cembrane diterpenoids and a promising cytotoxic agent. This target has a densely functionalized 14-membered carbocyclic structure, and presents an outstanding platform for the application of new synthetic methodologies. We propose to apply novel butenolide methodology and inverse demand hetero-Diels Alder chemistry, along with more established asymmetric epoxidation reactions to introduce the majority of the stereocenters present in 1. Completion of the synthesis will rely on substrate-directed diastereoselective transformations for the efficient generation of the remaining stereocenters, including the key macrocyclization event. Of the nine stereocenters in the anti-cancer agent peloruside A (2), we plan to introduce four through innovative ring-openings of enantiopure terminal epoxides. All but one of the remaining stereocenters will then be established by extending known catalytic, enantioselective methods to catalyst-controlled diastereoselective contexts. Colombiasin (3) and elisapterosin B are complex tetracyclic marine natural products incorporating two contiguous all carbon-stereogenic centers. We propose concise syntheses through application of asymmetric catalytic reactions discovered specifically for these targets to generate bicyclic quinone intermediates, followed by late stage intramolecular cycloaddition reactions. We propose to accomplish the first asymmetric catalytic synthesis of quinine (4), taking advantage of recently discovered asymmetric Michael addition and epoxidation methodologies to access this classic target in a concise and selective manner.